Silent progression in disease activity-free relapsing multiple sclerosis
Silent progression in disease activity-free relapsing multiple sclerosis
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DOI：
10.1002/ana.25463
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发表时间：
2019-05-01
影响因子：
11.2
通讯作者：
Hauser, Stephen L.
中科院分区：
文献类型：
--
作者：
Cree, Bruce A. C.;Hollenbach, Jill A.;Hauser, Stephen L.
目的：与治疗前自然史研究相比，积极治疗的患者恶化和进展为继发性进展型多发性硬化（MS）的发生率可能显著降低。尽管如此，在我们最近报道的前瞻性队列中，超过一半的复发性MS患者在随访第10年时累积了显著的新残疾。值得注意的是，2年时“无疾病活动证据”并不能预测长期稳定性。在这里，我们确定了临床复发和疾病活动的放射学证据在多大程度上有助于长期残疾积累。方法残疾进展定义为扩展残疾状态量表（EDSS）从基线EDSS = 0、1.0-5.0和5.5或更高分别增加1.5、1.0或0.5（或更高），从基线至第5年（+/- 1年）和持续至第10年（+/- 1年）进行评估。相对脑容量损失的纵向分析采用线性混合模型，以性别、年龄、病程和HLA-DRB 1 *15：01作为协变量。结果复发与1年内残疾的短暂增加相关（p = 0.012），但与确认的残疾进展无关（p = 0.551）。与那些保持稳定的人相比，残疾进展的人的相对脑体积下降速度更快（p < 0.05）。长期恶化在复发MS患者中很常见，在很大程度上与复发活动无关，并与加速脑萎缩相关。我们提出术语“沉默进展”来描述许多符合复发缓解型MS传统标准的患者中出现的隐性残疾。Ann Neurol 2019;85：653-666
Objective Rates of worsening and evolution to secondary progressive multiple sclerosis (MS) may be substantially lower in actively treated patients compared to natural history studies from the pretreatment era. Nonetheless, in our recently reported prospective cohort, more than half of patients with relapsing MS accumulated significant new disability by the 10th year of follow-up. Notably, "no evidence of disease activity" at 2 years did not predict long-term stability. Here, we determined to what extent clinical relapses and radiographic evidence of disease activity contribute to long-term disability accumulation. Methods Disability progression was defined as an increase in Expanded Disability Status Scale (EDSS) of 1.5, 1.0, or 0.5 (or greater) from baseline EDSS = 0, 1.0-5.0, and 5.5 or higher, respectively, assessed from baseline to year 5 (+/- 1 year) and sustained to year 10 (+/- 1 year). Longitudinal analysis of relative brain volume loss used a linear mixed model with sex, age, disease duration, and HLA-DRB1*15:01 as covariates. Results Relapses were associated with a transient increase in disability over 1-year intervals (p = 0.012) but not with confirmed disability progression (p = 0.551). Relative brain volume declined at a greater rate among individuals with disability progression compared to those who remained stable (p < 0.05). Interpretation Long-term worsening is common in relapsing MS patients, is largely independent of relapse activity, and is associated with accelerated brain atrophy. We propose the term silent progression to describe the insidious disability that accrues in many patients who satisfy traditional criteria for relapsing-remitting MS. Ann Neurol 2019;85:653-666